The following three lines of experimentation are proposed: (1) The definition of the molecular mechanisms of the regulation of transcription of the white locus of Drosophila melanogaster. These studies consist of a detailed physical analysis of white locus elements having apparent regulatory function as assessed by previous molecular and genetic studies. The proposed studies are directed at defining the physical relationship of these elements to the white locus transcription unit and at determining the effects of previously characterized white mutant alleles on the transcription of the locus. The transcription of the locus in wild type and mutant alleles at the locus will be analyzed and the function of white locus genetic elements will be investigated by in vitro mutagenesis and reintroduction of the locus by P element-mediated germline genetic transformation. (2) The test of a novel strategy for germline genetic transformation in Drosophila. The proposed method would allow the introduction of a Drosophila DNA segment at its locus of origin and would have several advantages over P element-mediated transformation. Several experiments are proposed to test and characterize this strategy. (3) The genetic and biochemical analysis of the zeste and suppressor-of-wa loci in Drosophila. By hypothesis, each of these loci is a developmental regulatory locus (one whose function is to regulate the developmental expression of other loci). Both of these loci are readily amenable to genetic manipulation and, in each case, at least one transcription unit presumed to be regulated by these loci is available in cloned form. Studies are proposed to test the hypothesis that these loci are regulatory and to define the nature and function of the products of the two loci.